1. Field of the Invention
The present disclosure relates to a modulator of vascular permeability using a pulsed laser and a method for modulating vascular permeability using the same.
2. Description of the Related Art
Because a drug administered into the blood vessel must cross the vascular wall to reach a desired target, vascular permeability has become a major consideration in drug development. In particular, in the case of an organ such as brain or retina in which a blood-brain barrier or blood-retina barrier is present, most drug candidates cannot cross the vascular wall, which has been a major constraint for drug development. Thus, a drug delivery system, with which a drug may cross the vascular wall effectively, is required.
In order to circumvent inefficiency problems related to drug delivery through permeation of the vascular wall, various methods have been suggested. Transcranial delivery is an approach that drills a hole in the skull and injects drugs intracerebrally or intracerebroventricularly. This method is viewed as a novel target route being developed for central nervous system drugs, but is disadvantageous in that it is very invasive. Furthermore, transnasal delivery is an approach to traverse the nasal mucosal barrier and inject drugs, but is limited only to low-molecular weight lipid soluble drugs. In addition, although there is an approach to chemically modify drugs and inject them, such as enhancing lipid solubility and lowering molecular weight, or taking advantage of an endogenous transporter-mediated process, there is no method that allows non-invasive and local delivery of high-molecular weight drugs into a target region.
A laser light source is one that emits photons in a coherent light beam. A typical laser is a monochromatic color, i.e., it has only one wavelength or color. Most light sources emit a large number of incoherent lights waves across a broad wavelength spectrum over a wide area. However, a laser beam is generally thin, and does not diffuse. In addition to its uses duet to its intrinsic light characteristics, the applications of laser have been extended to various areas such as industry, medical care, nuclear fusion, instrumentation, information memory, and optical communications. Lasers may be largely classified into pulsed and continuous wave types. When laser transition occurs not so much continuously but simultaneously, laser lasts for a short time and becomes a pulsed laser. While a continuous wave laser is used to continuously produce high heat, a pulsed laser is used when a strong and instantaneous energy burst is required.
In particular, near-infrared femtosecond pulsed lasers have been widely used for in vivo imaging due to their deep tissue penetration, reduced scattering, and localized nonlinear absorption. These advantages have also allowed for various optical modulations of live cells and tissues in a living animal, such as production of intracellular calcium, dissection of intracellular organelles, gene transformation, construction of a stroke animal model, acceleration of nerve firing, and blood flow inhibition. Methods for constructing an animal model of blood vessel rupture have been reported (N, Nishimura, et al., Nature methods, 2006, vol. 3, no. 2, pp. 99-108). Irradiation of an amplified 1 KHz pulsed laser can induce targeted insult to the cerebral cortical vascular wall, such as hemorrhage, intravascular clot formation or vascular extravasation, and laser induced vascular extravasation resulted in insult to the blood brain barrier (BBB). A method for disrupting a target blood vessel using an ultra-short pulsed laser (U.S. Pat. No. 7,258,687) and a method for administering a drug transdermally (U.S. Pat. No. 6,251,099) have been reported, but modulation of vascular permeability using an ultra-short pulsed laser has not been reported. Therefore, studies on optical modulation methods of vascular permeability, which are not accompanied by irreversible vascular damage, are needed.
Thus, the present inventors have studied an optical method for modulating vascular permeability to effectively deliver a drug in vivo into a target region, and confirmed that a device and a method for modulating vascular permeability may be usefully used to effectively deliver a material to be administered in vivo into a target region because a near-infrared femtosecond pulsed laser, which is low in heat loss with respect to tissues, non-invasive, and non-linear, effectively induces vascular permeability, thereby leading to completion of the present invention.